The effect of hypoxemia on muscle sympathetic nerve activity and cardiovascular function - a systematic review and meta-analysis

We conducted a meta-analysis to determine the effect of acute poikilocapnic, high-altitude, and acute isocapnia hypoxemia on muscle sympathetic nerve activity (MSNA) and cardiovascular function. A comprehensive search across electronic databases was performed until June 2021. All observational designs were included: population (healthy individuals); exposures (MSNA during hypoxemia); comparators (hypoxemia severity and duration); outcomes (MSNA; heart rate, HR; and mean arterial pressure, MAP). Sixty-one studies were included in the meta-analysis. MSNA burst frequency increased by a greater extent during high-altitude hypoxemia (P<0.001; mean difference (MD), +22.5 bursts/min; C.I.=-19.20-25.84), compared to acute poikilocapnic hypoxemia (P<0.001; MD, +5.63 bursts/min; C.I.=-4.09-7.17) and isocapnic hypoxemia (P<0.001; MD, +4.72 bursts/min; C.I.=-3.37-6.07). MSNA burst amplitude was only elevated during acute isocapnic hypoxemia (P=0.03; standard MD, +0.46 a.u.; C.I.=-0.03-0.90), and MSNA burst incidence was only elevated during high-altitude hypoxemia (P<0.001; MD, 33.05 bursts/100hb.; C.I.=-28.59-37.51). Meta-regression analysis indicated a strong relationship between MSNA burst frequency and hypoxemia severity for acute isocapnic studies (P<0.001), but not acute poikilocapnia (P=0.098). HR increased by the same extent across each type of hypoxemia (P<0.001; MD +13.81 heart beats (hb)/min; 95% C.I.=12.59-15.03). MAP increased during high-altitude hypoxemia (P<0.001; MD, +5.06 mmHg; C.I.=3.14-6.99), and acute isocapnic hypoxemia (P<0.001; MD, +1.91 mmHg; C.I.=0.84-2.97), but not acute poikilocapnic hypoxemia (P=0.95). Both hypoxemia type and severity influenced sympathetic nerve and cardiovascular function. These data are important for the better understanding of healthy human adaptation to hypoxemia.